MicroRNA-30a downregulation contributes to chemoresistance of osteosarcoma cells through activating Beclin-1-mediated autophagy

Xu,Ruida; Liu,Shuzhong; Chen,Haihong; Lao,Lifeng

doi:10.3892/or.2015.4497

MicroRNA-30a downregulation contributes to chemoresistance of osteosarcoma cells through activating Beclin-1-mediated autophagy

Authors:
- Ruida Xu
- Shuzhong Liu
- Haihong Chen
- Lifeng Lao
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Affiliations: Department of Orthopaedic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P.R. China
Published online on: December 18, 2015 https://doi.org/10.3892/or.2015.4497
Pages: 1757-1763

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Abstract

Autophagy has been recognized as an important element of tumor cell migration, invasion, and chemoresistance, and our previous results showed that Beclin-1-mediated autophagy contributed to osteosarcoma chemoresistance. However, the regulating mechanism of autophagy is still unclear. In this study, our aim was to clarify microRNA (miRNA)-related mechanisms underlying Beclin-1-mediated autophagy followed by chemotherapy in osteosarcoma. First, miRNA screening using qRT-PCR identified that miR-30a was significantly reduced in Dox-resistant osteosarcoma cells. Second, the autophagy activity in Dox-resistant increased while miR-30a expression reduced after chemotherapy agents as indicated by the enhanced expression of Beclin-1, the increased conversion of microtubule-associated protein LC3-I to LC3-II. Furthermore, overexpression of miR-30a significantly promoted chemotherapy-induced apoptosis and reduced autophagy activity responding to chemotherapy. Moreover, rapamycin, an autophagy promoter was able to partly reverse the effect of miR-30a and Luciferase reporter assay identified that miR-30a directly binds to the 3'-UTR of Beclin-1 gene, which further confirmed that miR-30a reduced chemoresistance via suppressing Beclin-1-mediated autophagy. Collectively these results indicate miR-30a and its downstream target gene Beclin-1 can be used in treatment of osteosarcoma chemoresistance in the future.

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